PUBLICATION
Meis cofactors control HDAC and CBP accessibility at Hox-regulated promoters during zebrafish embryogenesis
- Authors
- Choe, S.K., Lu, P., Nakamura, M., Lee, J., and Sagerström, C.G.
- ID
- ZDB-PUB-091101-11
- Date
- 2009
- Source
- Developmental Cell 17(4): 561-567 (Journal)
- Registered Authors
- Choe, Seong-Kyu, Nakamura, Mako, Sagerström, Charles
- Keywords
- DEVBIO
- MeSH Terms
-
- DNA-Binding Proteins/genetics
- DNA-Binding Proteins/metabolism
- Histone Deacetylases/genetics*
- Histone Deacetylases/metabolism
- Luciferases/metabolism
- PubMed
- 19853569 Full text @ Dev. Cell
Abstract
Hox proteins form complexes with Pbx and Meis cofactors to control gene expression, but the role of Meis is unclear. We demonstrate that Hoxb1-regulated promoters are highly acetylated on histone H4 (AcH4) and occupied by Hoxb1, Pbx, and Meis in zebrafish tissues where these promoters are active. Inhibition of Meis blocks gene expression and reduces AcH4 levels at these promoters, suggesting a role for Meis in maintaining AcH4. Within Hox transcription complexes, Meis binds directly to Pbx and we find that this binding displaces histone deacetylases (HDACs) from Hoxb1-regulated promoters in zebrafish embryos. Accordingly, Pbx mutants that cannot bind Meis act as repressors by recruiting HDACs and reducing AcH4 levels, while Pbx mutants that bind neither HDAC nor Meis are constitutively active and recruit CBP to increase AcH4 levels. We conclude that Meis acts, at least in part, by controlling access of HDAC and CBP to Hox-regulated promoters.
Genes / Markers
Figure Gallery (1 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping